Since the discovery of the fullerenes, carbon nanotubes, and graphene, single-walled materials have attracted rapidly growing interests over the past few decades. Such atomically thin materials possess astonishing properties that are vastly different from the corresponding bulk materials, suggesting a nearly limitless range of applications. Recently, the strong interest also expanded to non-carbon materials, such as boron nitride, molybdenum disulphide, and silicene.
Besides the unusual electronic properties, there is a strong interest in the applications of singled-walled materials, particularly in the delivery of therapeutic agents for medical purposes. For efficient delivery of an agent to the intended target, drug encapsulation and signalled release are crucial to control the drug degradation, overcome the transport barrier, and isolate the harmful side effects. Single-walled material is an optimal choice because of the minimal residue requiring cleaning-up from the body after the release of the drug. However, explorations using fullerenes and carbon nanotubes have focused on the loading of biomolecules on the exterior.
Nanocapsules are a promising new technology for advanced drug delivery. A highly sought-after capability is the controlled drug release from such capsules through external stimuli for pin-point accuracy in diseases therapy, where a thin, impermeable capsule shell that is sensitive to such stimuli is crucial. Techniques to fabricate truly impermeable single-walled capsules with controllable release are still lacking, despite a large body of works in inorganic capsules, liposomes, and polymersomes. A number of release controls were studied, including pH, redox reactions, enzymes, photons, and ultrasound. Ultrasound is particularly versatile and useful means for release control compared to optical and chemical stimuli because of its accurate localization, deep penetration in tissues, local release, and well established safety guidelines. Polymer-based capsules, the vast majority of the techniques studied for this purpose, has not been very effective due to their permeable nature and, where coupled with an ultrasound-based drug release, due to requirement for relatively high acoustic power.
In recent years, hollow silica nanospheres have been developed and used in several areas such as catalysis, imaging or drug controlled release. Preparation of hollow silica nanospheres method is generally performed in two steps, mainly making use of a template, wherein the template material may be a polymer latex, emulsion droplets, inorganic nanoparticles, polymer aggregates or complexes, and surfactant micelles. This multi-step preparation process causes high costs as well as environmental and energy consumption issues; moreover, high temperature calcination and chemical etching to remove the template can damage the core-shell silica, as well as the compounds included in the material.
For instance, CN101121519 describes a technique to fabricate porous hollow silica spheres with a smaller, movable, solid silica sphere core inside. The silica shell has a diameter of 100-1000 nm and a thickness of 20-200 nm with pores of 3-10 nm. The internal silica core is 50-600 nm in diameter. The fabrication procedure include: 1. synthesize the core silica spheres; 2. deposit an organic-inorganic hybrid middle layer on top of the core spheres; 3. coat a porous silica layer outside the middle layer; 4. Etch out the middle layer material to obtain the porous hollow silica spheres with a smaller silica core sphere. Cargo loading was achieved by diffusing drug content through the pores on the shell. The invention further describes an application of extended drug release using the said hollow spheres.
CN102583400 describes a technique to fabricate porous silica hollow spheres with a diameter of 100-1000 nm and a pore size of 2.5-3.5 nm. The procedure involves the ammonia-catalyzed hydrolysis-condensation reaction of tetraethyl orthosilicate (or a similar compound like tetrapropyl orthosilicate) in ethanol (or similar solvent like propanol) with the presence of a surfactant, followed by a calcination step to remove the surfactant component.
WO 2009/023697 describes a method for preparing hollow silica sphere comprising depositing silica-shell precursor on polyamino acid/carboxylate functionalized template particle under neutral condition to give core-shell spheres and removing the template particle by calcination. The method uses commercial polystyrene beads and their amine of carboxylate functionalized derivatives as template or polyamine or polyamino acid template. Hollow silica nanospheres have uniform, stable shell walls with defined porosity and narrow size distribution. The method allows for large scale preparation of the hollow nanoparticles with controlled size of 40 nm to 1 μm. The porosity of the silica shell is convenient for loading and releasing of drugs or used to contain a heavy element (e.g. metal nanoparticle) or magnetic oxides for X-ray or magnetic contrast reagents. The surface of the hollow silica shell is easily functionalized by grafting biofunctional groups that may combine with targeting proteins, antibodies, cells or tissues.
A plethora of other prior art documents including WO 2014/052911, CN103551093, CN103570027A, CN103585938, CN103803565, CN103833040 describe similar compounds and methods for preparing the same. Despite the large amount of work in the field, single layered silica materials, organic or inorganic, arranged in the form of flat surfaces or hollow nanospheres/nanocapsules, possibly having improved features, are needed, as well as rapid and reliable methods for preparing the same.